tbuckley/cabot-search huggingface dataset:
Toxicity risk score and clinical decline after adjuvant chemotherapy in older breast cancer survivors
Authors: Jingran Ji, Can-Lan Sun, Harvey J Cohen, Hyman B Muss, Marie Bae, Mina S Sedrak
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown. Methods In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high). We measured patient health status before (T1) and after (T2) chemotherapy using a clinical frailty index (Deficit Accumulation Index, categorized as robust, prefrail, and frail). The population of interest was robust women at T1. The primary outcome was decline in health status after chemotherapy, defined as a decline in Deficit Accumulation Index from robust at T1 to prefrail or frail at T2. Multivariable logistic regression was used to examine the association between T1 CARG-BC score and decline in health status, adjusted for sociodemographic and clinical characteristics. Results Of the 348 robust women at T1, 83 (24%) experienced declining health status after chemotherapy, of whom 63% had intermediate or high CARG-BC scores. After adjusting for sociodemographic and clinical characteristics, women with intermediate (odds ratio = 3.14, 95% confidence interval = 1.60 to 6.14, P &amp;lt; .001) or high (odds ratio = 3.80, 95% confidence interval = 1.35 to 10.67, P = .01) CARG-BC scores had greater odds of decline in health status compared with women with low scores. Conclusions In this cohort of older women with early breast cancer, higher CARG-BC scores before chemotherapy were associated with decline in health status after chemotherapy independent of sociodemographic and clinical risk factors.
Adaptation of Antarctic Icefish Vision to Extreme Environments
Authors: Gianni M Castiglione, Frances E Hauser, Alexander Van Nynatten, Belinda S W Chang
Journal: Molecular Biology and Evolution (2023)

Abstract Extreme environments, such as Antarctic habitats, present major challenges for many biological processes. Antarctic icefishes (Crynotothenioidea) represent a compelling system to investigate the molecular basis of adaptation to cold temperatures. Here, we explore how the sub-zero habitats of Antarctic icefishes have impacted rhodopsin (RH1) function, the temperature-sensitive dim-light visual pigment found in rod photoreceptors. Using likelihood models and ancestral reconstruction, we find that accelerated evolutionary rates in icefish RH1 underlie unique amino acid mutations absent from other deep-dwelling fishes, introduced before (S160A) and during (V259M) the onset of modern polar conditions. Functional assays reveal that these mutations red-shift rhodopsin spectral absorbance, consistent with spectral irradiance under sea ice. These mutations also lower the activation energy associated with retinal release of the light-activated RH1, and accelerate its return to the dark state, likely compensating for a cold-induced decrease in kinetic rates. These are adaptations in key properties of rhodopsin that mediate rod sensitivity and visual performance in the cold dark seas of the Antarctic.
A Combination of Autoantibodies Predicts the Fate of <scp>Cancer‐Associated</scp> Dermatomyositis
Authors: Manabu Fujimoto
Journal: Arthritis & Rheumatology (2023)

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The concomitant use of proton pump inhibitors and BRAF/MEK inhibitors in metastatic melanoma
Authors: Florence Poizeau, Frédéric Balusson, Florian Lemaitre, Camille Tron, Marc Pracht, David Russo, Monica Dinulescu, Thierry Lesimple, Emmanuel Oger, Alain Dupuy
Journal: British Journal of Dermatology (2023)

Abstract Background Proton-pump inhibitors (PPIs) are commonly used by patients with cancer, although they could reduce the absorption of oral anticancer targeted therapies. The US Food and Drug Administration states that the effect of PPIs on the efficacy of dabrafenib use by patients with metastatic melanoma is unknown. As a precautionary measure, the European Society for Medical Oncology recommends avoiding PPIs for patients receiving dabrafenib. Objectives To determine the effect of the concomitant use of PPIs and BRAF/MEK inhibitors in patients with metastatic melanoma. Methods Patients with advanced melanoma receiving BRAF/MEK inhibitors as first-line treatments between 2015 and 2017 in France were selected using the French National Health Insurance database. We compared time-to-treatment discontinuation (TTD) and overall survival (OS) according to concomitant PPI exposure. We balanced the baseline characteristics of patients exposed and nonexposed to PPIs using an overlap weighting method based on a propensity score. Results The metastatic melanoma cohort comprised 1028 patients receiving BRAF/MEK inhibitors, including 361 (35.1%) patients using PPIs. PPI users had more comorbidities and a more severe metastatic disease. After having equally distributed metastatic sites and comorbidities across patients exposed and nonexposed to PPIs, concomitant PPI use was not associated with shorter TTD [weighted hazard ratio (wHR) 1.03, 95% confidence interval (CI) 0.86–1.24] or OS (wHR 1.11, 95% CI 0.88–1.39). Consistent results were observed when restricting the population to patients receiving dabrafenib, or when narrowing exposure to PPIs with stronger inhibition of cytochromes. Conclusions In a population-based cohort of patients with advanced melanoma, the concomitant use of PPIs and BRAF/MEK inhibitors was not associated with worse outcome.
Clinical Connections
Journal: Arthritis & Rheumatology (2023)

Approximately two-thirds of rheumatoid arthritis (RA) cases are characterized by circulating autoantibodies against the Fc part of IgG (rheumatoid factors) and against proteins subjected to different types of posttranslational modifications, such as citrullination, carbamylation, acetylation, or malondialdehyde modification.Such humoral autoimmunity typically precedes RA onset by several years, suggesting a role for the circulating autoantibodies in early steps of disease progression.The presence of anti-citrullinated protein antibodies (ACPAs) in the blood indicates an increased risk of future RA development and ACPA-positive but still RA-free individuals are frequently characterized by ar thralgia, bone erosion, and, closer to disease onset, the development of tenosynovitis.Krishnamurthy et al examined whether ACPAs could play a role in these symptoms by isolating ACPA clones from the joint of an RA patient and injecting these (as murinized IgG2a) in otherwise healthy mice.Importantly, the injected antibodies induced pain-like behavior, bone erosion, and tenosynovitis in mice, recapitulating the symptoms observed in ACPA-positive individuals at risk of RA.Although ACPAs typically cross-react with other types of protein modifications as well, the observed effects were largely dependent on the protein arginine deiminase 4 (PAD4) enzyme, suggesting the importance of protein citrullination in the ACPA-mediated pathways.ACPAs may thus be responsible for certain symptoms that precede RA onset.However, as patient-derived ACPA preparations have so far failed to trigger arthritis in animal models, a key question that has remained is how these antibodies actually contribute to joint pathologies in established RA. KEY POINTS• Arthralgia, tenosynovitis, and microscopical bone erosions can precede RA onset in ACPA-positive individuals.• These symptoms were recapitulated by injecting patient-derived ACPA clones into otherwise healthy mice.• ACPA-mediated, pain-like behavior, bone loss, and tenosynovitis were largely dependent on the PAD4 enzyme, suggesting a key role for protein citrullination in the autoantibody-induced pathways.• Experimental models could help clarify early pathogenic mechanisms that precede RA onset and, potentially, the evaluation of preventive strategies.
Unpaired mesh-to-image translation for 3D fluorescent microscopy images of neurons
Authors: Mihael Cudic, Jeffrey S. Diamond, J. Alison Noble
Journal: Medical Image Analysis (2023)

While Generative Adversarial Networks (GANs) can now reliably produce realistic images in a multitude of imaging domains, they are ill-equipped to model thin, stochastic textures present in many large 3D fluorescent microscopy (FM) images acquired in biological research. This is especially problematic in neuroscience where the lack of ground truth data impedes the development of automated image analysis algorithms for neurons and neural populations. We therefore propose an unpaired mesh-to-image translation methodology for generating volumetric FM images of neurons from paired ground truths. We start by learning unique FM styles efficiently through a Gramian-based discriminator. Then, we stylize 3D voxelized meshes of previously reconstructed neurons by successively generating slices. As a result, we effectively create a synthetic microscope and can acquire realistic FM images of neurons with control over the image content and imaging configurations. We demonstrate the feasibility of our architecture and its superior performance compared to state-of-the-art image translation architectures through a variety of texture-based metrics, unsupervised segmentation accuracy, and an expert opinion test. In this study, we use 2 synthetic FM datasets and 2 newly acquired FM datasets of retinal neurons.
Identifying RNA Modifications by Direct RNA Sequencing Reveals Complexity of Epitranscriptomic Dynamics in Rice
Authors: Feng Yu, Huanhuan Qi, Li Gao, Sen Luo, Rebecca Njeri Damaris, Yinggen Ke, Wenhua Wu, Pingfang Yang
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Transcriptome analysis based on high-throughput sequencing of a cDNA library has been widely applied to functional genomic studies. However, the cDNA dependence of most RNA sequencing techniques constrains their ability to detect base modifications on RNA, which is an important element for the post-transcriptional regulation of gene expression. To comprehensively profile the N 6 -methyladenosine (m6A) and N 5 -methylcytosine (m5C) modifications on RNA, direct RNA sequencing (DRS) using the latest Oxford Nanopore Technology was applied to analyze the transcriptome of six tissues in rice. Approximately 94 million reads were generated, with an average length ranging from 619 nt to 1013 nt, and a total of 45,707 transcripts across 34,763 genes were detected. Expression profiles of transcripts at the isoform level were quantified among tissues. Transcriptome-wide mapping of m6A and m5C demonstrated that both modifications exhibited tissue-specific characteristics. The transcripts with m6A modifications tended to be modified by m5C, and the transcripts with modifications presented higher expression levels along with shorter poly(A) tails than transcripts without modifications, suggesting the complexity of gene expression regulation. Gene Ontology analysis demonstrated that m6A- and m5C-modified transcripts were involved in central metabolic pathways related to the life cycle, with modifications on the target genes selected in a tissue-specific manner. Furthermore, most modified sites were located within quantitative trait loci that control important agronomic traits, highlighting the value of cloning functional loci. The results provide new insights into the expression regulation complexity and data resource of the transcriptome and epitranscriptome, improving our understanding of the rice genome.
Whole-Genome Duplication Reshaped Adaptive Evolution in a Relict Plant Species, <i>Cyclocarya Paliurus</i>
Authors: Yinquan Qu, Xulan Shang, Ziyan Zeng, Yanhao Yu, Guoliang Bian, Wenling Wang, Li Liu, Li Tian, Shengcheng Zhang, Qian Wang, Dejin Xie, Xuequn Chen, Zhenyang Liao, Yibin Wang, Jian Qin, Wanxia Yang, Caowen Sun, Xiangxiang Fu, Xingtan Zhang, Shengzuo Fang
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently. Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B. Here, we presented three C. paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly. Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids. Re sequencing analysis of 45 C. paliurus individuals uncovered two bottlenecks, consistent with the known events of environmental changes, and many selectively swept genes involved in critical biological functions, including plant defense and secondary metabolite biosynthesis. We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes, in particular gibberellin-related genes, associated with the heterodichogamy in C. paliurus species. Our study sheds light on evolutionary history of C. paliurus and provides genomic resources to study the medicinal herbs.
Long-term effectiveness of COVID-19 vaccines against infections, hospitalisations, and mortality in adults: findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022
Authors: Nana Wu, Keven Joyal-Desmarais, Paula A B Ribeiro, Ariany Marques Vieira, Jovana Stojanovic, Comfort Sanuade, Doro Yip, Simon L Bacon
Journal: The Lancet Respiratory Medicine (2023)
Lipid nanoparticle-based ribonucleoprotein delivery for in vivo genome editing
Authors: Haruno Onuma, Yusuke Sato, Hideyoshi Harashima
Journal: Journal of Controlled Release (2023)

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system is a technology that is used to perform site-specific gene disruption, repair, and the modification of genomic DNA via DNA repair mechanisms, and is expected to be a fundamental therapeutic strategy for the treatment of infectious diseases and genetic disorders. For clinical applications, the non-viral vector-based delivery of the CRISPR/Cas ribonucleoprotein (RNP) is important, but the poor efficiency of delivery and the lack of a practical method for its manufacture remains as an issue. We report herein on the development of a lipid nanoparticle (LNP)-based Cas RNP delivery system based on optimally designed single stranded oligonucleotides (ssODNs) that allow efficient in vivo genome editing. The formation of sequence-specific RNP-ssODN complexes was found to be important for the functional delivery of RNP. Furthermore, the melting temperature (Tm) between sgRNA and ssODN had a significant effect on in vivo gene knockout efficiency. An ssODN with a high Tm resulted in limited knockout (KO) activity while that at near room temperature showed the highest KO activity, indicating the importance of the cytosolic release of RNPs. Two consecutive intravenous injections of the Tm optimized formulation achieved approximately 70% and 80% transthyretin KO at the DNA and protein level, respectively, without any obvious toxicity. These findings represent a significant contribution to the development of safe in vivo CRISPR/Cas RNP delivery technology and its practical application in genome editing therapies.
The therapeutic potential of psychedelics: the European regulatory perspective
Authors: Florence Butlen-Ducuing, Drummond E-Wen McCulloch, Marion Haberkamp, Taina Mattila, Ewa Bałkowiec-Iskra, Georgios Aislaitner, Pavel Balabanov, Johan Lundberg, Dea Siggaard Stenbæk, Andre Elferink, Gitte M Knudsen, Steffen Thirstrup
Journal: The Lancet (2023)
Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study
Authors: Neil R Aggarwal, Kyle C Molina, Laurel E Beaty, Tellen D Bennett, Nichole E Carlson, David A Mayer, Jennifer L Peers, Seth Russell, Matthew K Wynia, Adit A Ginde
Journal: The Lancet Infectious Diseases (2023)
Scaling up evidence-based approaches to tuberculosis screening in prisons
Authors: Salome Charalambous, Kavindhran Velen, Zulma Rueda, Julio Croda, Michael E Herce, Sheela V Shenoi, Frederick L Altice, Monde Muyoyeta, Lily Telisinghe, Louis Grandjean, Salmaan Keshavjee, Jason R Andrews
Journal: The Lancet Public Health (2023)

People deprived of liberty have among the highest rates of tuberculosis globally. The incidence of tuberculosis is ten times greater than the incidence of tuberculosis in the general population. In 2021, WHO updated its guidance to strongly recommend systematic screening for tuberculosis in prisons and penitentiary systems. Which case-finding strategies should be adopted, and how to effectively implement these strategies in these settings, will be crucial questions facing ministries of health and justice. In this Viewpoint, we review the evidence base for tuberculosis screening and diagnostic strategies in prisons, highlighting promising approaches and knowledge gaps. Drawing upon past experiences of implementing active case-finding and care programmes in settings with a high tuberculosis burden, we discuss challenges and opportunities for improving the tuberculosis diagnosis and treatment cascade in these settings. We argue that improved transparency in reporting of tuberculosis notifications and outcomes in prisons and renewed focus and resourcing from WHO and other stakeholders will be crucial for building the commitment and investments needed from countries to address the continued crisis of tuberculosis in prisons.
When I use a word . . . . The New Sydenham Society Lexicon
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

After successfully publishing 80 volumes of medical texts, the New Sydenham Society embarked on the production of a medical lexicon, based on an earlier work, Robert Gray Mayne’s <i>Expositional Lexicon</i>. The task proved more difficult than the society had anticipated; it took 21 years and the publication of 25 fascicles, later combined into five large volumes, and it put great financial stress on the society. The later publication of the <i>Atlas of Clinical Medicine</i>, in 27 fascicles, was the final nail in the society’s financial coffin. Nevertheless, the <i>New Sydenham Society’s Lexicon of Medicine and the Allied Sciences</i> is an important publication in the history of medical lexicography. It has provided over 2000 instances for citation in the <i>Oxford English Dictionary</i>, of which about 480 are earliest, and often sole, citations.
Impact of Intrahepatic External Beam Radiotherapy in Advanced Hepatocellular Carcinoma Patients Treated with Tyrosine Kinase Inhibitors
Authors: Myung Ji Goh, Hee Chul Park, Jeong Il Yu, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Dong Hyun Sinn, Moon Seok Choi
Journal: Liver Cancer (2023)

We aimed to investigate whether concurrent use of intrahepatic external beam radiotherapy (EBRT) is a viable option for patients with advanced hepatocellular carcinoma (HCC) undergoing tyrosine kinase inhibitor (TKI) therapy.A total of 453 patients with Barcelona Clinic Liver Cancer stage C (BCLC C) HCC, who started first-line treatment with TKI with intrahepatic EBRT (TKI + RT, n = 97) or TKI without intrahepatic EBRT (TKI, n = 356) were analyzed. The overall survival (OS) and progression-free survival (PFS) were compared in the overall cohort, patients who received at least 8 weeks of TKI treatment and a propensity score-matched cohort.OS and PFS were better in those treated with TKI + RT than TKI (8.6 vs. 4.4 months and 4.5 vs. 2.3 months, respectively, with p < 0.001). Of note, the TKI + RT group demonstrated significantly longer time to intrahepatic tumor progression. In subgroup analysis, TKI + RT led to better OS than TKI in all subgroups and PFS was significantly improved in patients without extrahepatic metastasis and those with portal vein invasion. There was no significant difference in treatment discontinuation due to adverse events between the TKI + RT and TKI groups (32.0% vs. 37.9%, p = 0.34). Furthermore, patients treated with TKI + RT showed better liver function preservation over time compared to TKI without intrahepatic EBRT. Comparable treatment outcomes were observed between patients who received at least 8 weeks of TKI treatment and the propensity score-matched cohort.Concurrent intrahepatic EBRT targeting the liver and/or macrovascular invasion can be a viable option to improve outcomes of BCLC stage C patients receiving TKI therapy with an aim to control intrahepatic progression and preserving the liver function.
We need to talk about nonprobability samples
Authors: Robin J. Boyd, Gary D. Powney, Oliver L. Pescott
Journal: Trends in Ecology & Evolution (2023)

In most circumstances, probability sampling is the only way to ensure unbiased inference about population quantities where a complete census is not possible. As we enter the era of 'big data', however, nonprobability samples, whose sampling mechanisms are unknown, are undergoing a renaissance. We explain why the use of nonprobability samples can lead to spurious conclusions, and why seemingly large nonprobability samples can be (effectively) very small. We also review some recent controversies surrounding the use of nonprobability samples in biodiversity monitoring. These points notwithstanding, we argue that nonprobability samples can be useful, provided that their limitations are assessed, mitigated where possible and clearly communicated. Ecologists can learn much from other disciplines on each of these fronts.
ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated <i>BRAF</i><sup>V600E</sup>-Mutant Metastatic Colorectal Cancer
Authors: Eric Van Cutsem, Julien Taieb, Rona Yaeger, Takayuki Yoshino, Axel Grothey, Evaristo Maiello, Elena Elez, Jeroen Dekervel, Paul Ross, Ana Ruiz-Casado, Janet Graham, Takeshi Kato, Jose C. Ruffinelli, Thierry André, Edith Carrière Roussel, Isabelle Klauck, Mélanie Groc, Jean-Claude Vedovato, Josep Tabernero
Journal: Journal of Clinical Oncology (2023)

The positive BEACON colorectal cancer (CRC) safety lead-in, evaluating encorafenib + cetuximab + binimetinib in previously treated patients with